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………………..…………………………………………………………………………………………………………………………………… Marijuana Science vs. Anecdote Steven C. Matson, MD, FASAM, FAAP Chief of Adolescent Medicine, Nationwide Children’s Hospital Associate Professor of Pediatrics, The Ohio State University College of Medicine Ohio Society for Public Health Education (OSOPHE) invites you to attend the annual Health Educators’ Institute (HEI) October 26, 2017

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MarijuanaScience vs. Anecdote

Steven C. Matson, MD, FASAM, FAAPChief of Adolescent Medicine, Nationwide Children’s Hospital

Associate Professor of Pediatrics, The Ohio State University College of Medicine

Ohio Society for Public Health Education (OSOPHE) invites you to attend the annual Health Educators’ Institute (HEI)

October 26, 2017

Disclosures

I believe legalization of Marijuana in any form is detrimental to the

public health of Americans.Especially Adolescents

Overview

• History of marijuana use

• Update latest research on medicinal marijuana

• Marijuana’s effects on humans

• Negative outcomes of marijuana use on adolescents

• Public health impact of legalization

History of Medical Marijuana

• Chinese Emperor Fu Hsi in 2900 BC made reference to Ma, the Chinese word for Cannabis

• Noting that Cannabis was a very popular medicine that possessed both yin and yang

History of Medical Marijuana

• 1450 BC, Exodus (30:22-23)

• Recipe for the anointing oil passed from God to Moses included cannabis, or kaneh-bosm in Hebrew.

History of Medical Marijuana

• 1 AD - Ancient Chinese text recommends marijuana > 100 ailments Gout Rheumatism Malaria Absentmindedness

• Marijuana depicted as an ideogram of plants drying in a shed.

Chinese ideogram formarijuana ("ma")

History of Medical Marijuana

• "The Jamestown settlers brought the marijuana plant, hemp, to North America in 1611

• Cannabis as a treatment for depression in 1621 book, The Anatomy of Melancholy.

History of Medical Marijuana

• 1840 - Medical Marijuana in United Kingdom via Dr. William O'Shaughnessy for Queen Victoria’s menstrual cramps

• 1850 - Marijuana added to US Pharmacopeia as treatment for multiple conditions

History of Medical Marijuana

• 1906 - Pure Food and Drugs Act requires labeling of medicine, including cannabis

• Feb. 19, 1925 - League of Nations sign multilateral treaty restricting cannabis use to scientific and medical only

History of Medical Marijuana

• 1960 Dr Raphael Mechoulamoriginated modern-day cannabinoid research

History of Medical Marijuana

• 1963 Chemical structure of marijuana cannabinoid cannabidiol (CBD) was discovered

• 1964 marijuana’s psychoactive cannabinoid delta-9-tertrahydrocannabinol (THC)

(THC)

History of Medical Marijuana

• 1970 - Controlled Substances Act classifies marijuana as a drug with "No Accepted Medical Use"

• 1974 - NIDA established, In charge of contracts to grow marijuana for research

Receptors for Marijuana in the Human Body?

• 1992: A normal body system was discovered, consisting of endogenous cannabinoid neurotransmitters and endocannabinoid receptors in multiple organs, such as the brain

Devane W. A., Hanus L., 992). Science 258, 1946–1949 10.1126/science.1470919

Nov. 5, 1996 - California Legalizes Medical Marijuana

Medical marijuana activist Chris Conrad and his wife Mikki Norris advocated for

the passage of Prop. 215

Limited Use (CBD oil, low THC)

Marijuana and Ohio

•November 2015: Ohio votes to not legalize marijuana

•May 2016 Ohio medical marijuana bill advances

Ohio Medical Marijuana Laws• June 08, 2016, Governor signed House Bill 523

allowing for the use of marijuana for medical reasons starting September 2018.

• Ohio Medical Marijuana Control Program, will administer and oversee the state’s program.

• Allows for the legal possession of a maximum of a 90-day supply of cannabis, by a qualified patient.

• Minors are able to receive medical marijuana.• Ohio has not approved smoking as a legal method

of delivery — only methods approved:OilsTincturesPlant materialPatches

Conditions That Are Allowed to be Treated with Medical Marijuana in Ohio

• Alzheimer’s Disease• Amyotrophic Lateral

Sclerosis (ALS), also know as Lou Gehrig’s disease

• Cancer• Chronic traumatic

encephalopathy• Crohn’s disease• Epilepsy• Fibromyalgia• Glaucoma• Hepatitis C• HIV-AIDS• Inflammatory bowel

disease (IBD)

• Chronic, severe, or intractable pain• Multiple sclerosis• Parkinson's disease• Post-Traumatic Stress Disorder• Sickle cell anemia• Spinal cord disease, or injury• Tourette Syndrome• Traumatic brain injury• Ulcerative colitis

Endocannabinoid Receptor Location, Probable Physiologic Function, and the Potential Effects of Marijuana

FDA Medical Marijuana• Medications approved Dronabinol (Marinol®) synthesized THC that is

approved for anorexia in HIV, also nausea and vomiting with chemotherapy Nabilone (Cesamet®) synthetic THC analog

approved for cancer chemotherapy nausea Nabiximols (Sativex®) A 1:1 mixture of the purified

marijuana plant constituents THC and cannabidiol(CBD) delivered in spray formulation. It is approved in several countries Canada, Europe for pain

management and spasticity in certain types of patients.

Marijuana as MedicineHill KP, JAMA. 2015;313(24):2474-2483

•Medical literature on medical marijuana was reviewed from 1948 to March 2015 via MEDLINE.

•Emphasis on 28 randomized clinical trials of cannabinoids as pharmacotherapy.

•Use of marijuana supported by high-quality evidence for:Chronic painNeuropathic painSpasticity due to multiple sclerosis is.

Marijuana as MedicineWhiting P. J Am Med Assoc. 2015;313:2456–73

• 28 databases and grey literature sources searched from inception to April 2015

• 79 studies (6462 subjects), available as 151 reports

Medical use of Cannabinoids in 3 Neurologic Disorders (Multiple Sclerosis, Epilepsy, And

Movement DisordersA Systematic Review of 65 Years by the

American Academy of Neurology

Koppel B. Neurology 2014;82:1556–63 Yadar V. Neurology. 2014;82:1083–92

Serious adverse events were more common in the cannabidiol group 16% vs. 5%

Medical Cannabinoid Evidence-Based Guidelines

Cochrane Reviews

Marshall K: Cochrane reviews. Rome: Cochrane Drugs and Alcohol Group, 2014.Gloss D: Cochrane reviews. Liverpool: Cochrane Epilepsy Group, 2014.Lutgee E: Cochrane reviews. London: Cochrane HIV/AIDS Group, 2013.

McLoughlin B: Cochrane reviews. London: Cochrane Schizophrenia Group, 2014.

Cannabis-Therapeutic Effects

• There is conclusive or substantial evidence that cannabis or cannabinoids are effective: For the treatment of chronic pain in adults

(cannabis) As anti-emetics in the treatment of

chemotherapy-induced nausea and vomiting (oral cannabinoids) For improving patient-reported multiple

sclerosis spasticity symptoms (oral cannabinoids)

Cannabis-Cancer• There is moderate evidence of no

statistical association between cannabis use and: Incidence of lung cancer (cannabis smoking)

(5-1) Incidence of head and neck cancers (5-2)

Cannabis-Injury and Death• There is substantial evidence of a

statistical association between cannabis use and: Increased risk of motor vehicle crashes (9-3)

• There is moderate evidence of a statistical association between cannabis use and: Increased risk of overdose injuries, including

respiratory distress, among pediatric populations in U.S. states where cannabis is legal (9-4b)

Cannabis-Birth Outcomes• There is substantial evidence of a

statistical association between maternal cannabis smoking and Lower birth weight of the offspring (10-2)

Cannabis-Psychosocial• There is moderate evidence of a statistical

association between cannabis use and: The impairment in the cognitive domains of

learning, memory, and attention (acute cannabis use)

• There is limited evidence of a statistical association between cannabis use and: Impaired academic achievement and education

outcomes (11-2) Increased rates of unemployment and/or low

income (11-3) Impaired social functioning or engagement in

developmentally appropriate social roles

Cannabis—Mental Health• There is substantial evidence of a statistical association

between cannabis use and: The development of schizophrenia or other psychoses, with

the highest risk among the most frequent users

• There is moderate evidence of a statistical association between cannabis use and: Better cognitive performance among individuals with

psychotic disorders and a history of cannabis use Increased symptoms of mania and hypomania in individuals

diagnosed with bipolar disorders (regular cannabis use) A small increased risk for the development of depressive

disorders Increased incidence of suicidal ideation and suicide attempts

with a higher incidence among heavier users Increased incidence of suicide completion Increased incidence of social anxiety disorder (regular

cannabis use)

Cannabis-Problem Use• There is substantial evidence that: Being male and smoking cigarettes are risk

factors for the progression of cannabis use to problem cannabis use Initiating cannabis use at an earlier age is a risk

factor for the development of problem cannabis use Increases in cannabis use frequency and the

progression to developing problem cannabis use

• There is moderate evidence of a statistical association between cannabis use and: The development of substance dependence

and/or a substance abuse disorder for substances including, alcohol, tobacco, and other illicit drugs

What Happens When You Use Marijuana?

Psychologic and Physiologic Effects

• Acute effects peak 30 minutes post smoking 1-6 hours after ingestion

• POSITIVE EFFECTS: Relaxation, euphoria, heightened perception Sociability, sensation of slowing time Increased appetite and decreased pain

• NEGATIVE EFFECTS: Paranoia, anxiety, irritability Impaired short term memory, poor attention and

judgement Hindered coordination and balance

Psychologic and Physiologic Effects

• PHYSIOLOGIC EFFECTS: Increased heart rate of 20-50 beats/min. Elevated blood pressure Bronchial relaxation Dry mouth and throat Conjunctival injection.

• Side Effects Worsened By: Strength of product Synthetic weed Adding cocaine, PCP, meth, to marijuana Experience of user

% of Students Who Used Tobacco or Marijuana One or More Times During

Past Month Ohio: 2003‐2013

% U

sed

http://www.odh.ohio.gov/odhPrograms/chss/ad_hlth/YouthRsk/youthrsk1.aspx

Annual Prevalence of Tobacco, Alcohol and Other Drug Use

12th Graders in 2016

Johnston, L. D., O’Malley, P. M., Bachman, J. G., & Schulenberg, J. E. (2016). Monitoring the Future national results on drug use: 2016 Overview, Key Findings on Adolescent Drug Use. Ann Arbor: Institute for Social Research, The University of Michigan.

% Using

Marijuana and Adolescents

• Most commonly used illicit drug• Growing body of evidence links use to adverse

short and long term outcomes• Legalization has led adolescents have a low

perception of risk of marijuana use.

• AAP, AMA, ASAM, AACAP identify marijuana as a public health concern and oppose legalization

MTF 2016

•9% of all users will become addicted•17% of teens that start smoking early•25 to 50% of daily marijuana smokers

Cannabis DSM-V

•Cannabis Intoxication DSM-V Clinically significant problematic behavioral Impaired motor coordination Euphoria, anxiety, sensation of slowed time Impaired judgment, social withdrawal ≥ 2 of the following: Conjunctival injection,

increased appetite, dry mouth, tachycardia

•Cannabis Use Disorder•Cannabis Withdrawal

Cannabis sativa Sativa plants are tall, loosely branched have long, narrow leaves. Usually grown outdoors and can reach heights of up to 20 feet.

Cannabis indica Indica plants are short, densely branched and have wider leaves. They are better suited for growing indoors.

Current Marijuana Use and Marijuana Use Disorder in

Adolescents and Young Adults Current Marijuana Users (Past month use)

Age (Years) Number % of Population Change

12-17 1,800,000 7.4% No Change

18-25 6,800,000 19.6% Increase

Adolescents and Young Adults with Marijuana Use Disorder

12-17 667,000 2.7% Decrease

18-25 1,700,000 4.9% No Change

2014 NSDUH

Prevalence of Marijuana Use Disorders in the United States

Between 2001-2002 and 2012-2013

• National Epidemiologic Survey on Alcohol and Related Conditions April 2001-April 2002; N = 43 093) April 2012-June 2013; N = 36 309)

• The past-year prevalence of marijuana use was: 4.1% in 2001-2002 9.5% in 2012-2013 (P < .05).

• The past-year prevalence of marijuana use disorder was: 1.5% in 2001-2002 2.9% in 2012-2013 (P < .05).

Hasin DS;JAMA Psychiatry Published online October 21, 2015

Age 12-17 years1,076,000

Age 18-25 years2,640,000

92% Need but NOTReceiving Treatment

91% Need but NOTReceiving Treatment

8% 9%

Receiving Treatment

Past Year Illicit Drug Dependence or Abuse

and Treatment by Age

Adolescent Brain Development

• Jay Giedd and colleagues at NIH has shown that the brain is still developing during adolescence and young adulthood.

• An excessive number of connections exist between brain cells prior to adolescence, but at about age 11 or 12, the brain begins the processing of “sculpting” or pruning-back a significant proportion.

Arborization and Pruning

• Neurons become bushier and make more/complex connections

• Then certain connections are eliminated or “pruned” Ultimately 40% are

eliminated

Use it or Lose it!!!

From: JN Geidd Ann N Y Acad Sci. 2004 Jun; 1021():77-85.

Anatomical Changes of Teen Brain

• Brain 90% of adult size by age 6

• However, various subcomponents undergo dynamic changes from 11-25 years White Matter Grey Matter

White Matter Changes

• Increases throughout childhood and adolescence

• White matter = myelinated axons

• Myelinated axons speeds up nerve transmission 100 times

• Greater speed = Cognitive complexity Combine information from various

sources

Gray Matter Changes

• In general, volume loss by end of adolescence:

• Two major categories Subcortical

Basal gangliaAmygdala and

Hippocampus

Cortical Gray Matter

Dorsolateral Prefrontal Cortex

• One of the last areas of the brain to mature

• Executive Functions: Planning Setting Priorities Organizing thoughts Suppressing impulses Weighing consequences

How Prolonged Cannabis Exposure During Adolescence Might Disrupt the

Functions of the Endocannabinoid System and Alter Brain Development

• Interfering with processes of synaptic pruning

• Altering the development of white matter

Interfering with processes of synaptic pruning (red pathway)

Altering the development of white matter (blue pathway)

The Earlier Teens Use Drugs The Greater the Risk of a

Substance Use Disorder28.1

18.6

7.4

4.3

0

5

10

15

20

25

30

< 15 15-17 18-20 > 21

% of Population 12 and Older with

a Substance Use Disorder

Age in Years≥

NSDUH

Young Adult Sequelae Of Adolescent Cannabis Use: An Integrative Analysis

N = 2537 to 3765

• Associations for depression and welfare dependence were both nonsignificant

• Adjusted ORs suggested that individuals who were daily users before age 17 years had odds of:High-school completion and degree attainment

that were 63% and 62% lower than those who had never used cannabisCannabis dependence that were 18 times higher,Use of other illicit drugs that were eight times

higherOdds of suicide attempt that were seven times

higherSilins E, www.thelancet.com/psychiatry Vol 1 September 2014

Adverse Effects of Short-Term Use & Long-Term or Heavy Use of MarijuanaVolkow ND: N Engl J Med. 2014 June 5; 370(23): 2219–2227

* The effect is strongly associated with initial marijuana useearly in adolescence.

Level of Confidence in the Evidence for Adverse Effects of Marijuana on

Health and Well-Being

*The indicated overall level of confidence in the association between marijuana use and the listed effects represents an attempt to rank the strength of the current evidence, especially with regard to heavy or long-term use and use that starts in adolescence.

What Happens When States Legalize Marijuana?

Average Past Month Use by 12-17 Year Olds

United States 2013/2014

0

2

4

6

8

10

12

Non-MedicalMarijuana State

Medical MarijuanaStates

Recreational/MedicalMarijuana States

2013/2014 NSDUH

Perc

ent U

sing

Average Past Month Use by 18-25 Year Olds

United States 2013/2014

0

5

10

15

20

25

30

Non-MedicalMarijuana State

Medical MarijuanaStates

Recreational/MedicalMarijuana States

2013/2014 NSDUH

Perc

ent U

sing

SAMHSA.gov, National Survey on Drug Use and Health 2013 and 2014

Effect on Adolescent Scholastics

Colorado Student Marijuana Source 2015 and 2016

Colorado Association of School Resource Officers (CASRO) and Rocky Mountain HIDTA

05

101520253035404550

Medical MarijuanaCard Holders

Retail MarijuanaStores

Medical MarijuanaDispensaries

Parents Black Market Friend WhoObtained it Legally

2015 2016

Perc

ent

Conclusions• Legalization of recreational and medical

marijuana increases marijuana use in teens and adults.

• Early and heavy marijuana use in adolescence leads to negative outcomes that may be due to permanent changes in the brain

• Medical marijuana has some documented medical indications.

• States that have increased access to marijuana have increased negative outcomes and even deaths